PMID- 33519498
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210202
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 11
DP  - 2020
TI  - Melatonin Lowers HIF-1alpha Content in Human Proximal Tubular Cells (HK-2) Due to 
      Preventing Its Deacetylation by Sirtuin 1.
PG  - 572911
LID - 10.3389/fphys.2020.572911 [doi]
LID - 572911
AB  - Although melatonin is widely known for its nephroprotective properties, there are 
      no reports clearly pointing at its impact on the activity of hypoxia-inducible 
      factor-1 (HIF-1), the main mediator of metabolic responses to hypoxia, in 
      kidneys. The aim of the present study was to elucidate how melatonin affects the 
      expression of the regulatory subunit HIF-1alpha in renal proximal tubules. HK-2 
      cells, immortalized human proximal tubular cells, were cultured under hypoxic 
      conditions (1% O(2)). Melatonin was applied at 100 muM concentration. Protein and 
      mRNA contents were determined by Western blot and RT-qPCR, respectively. HIF-1alpha 
      acetylation level was established by means of immunoprecipitation followed by 
      Western blot. Melatonin receptors MT1 and MT2 localization in HK-2 cells was 
      visualized using immunofluorescence confocal analysis. It was found that 
      melatonin in HK-2 cells (1) lowered HIF-1alpha protein, but not mRNA, content; (2) 
      attenuated expression of HIF-1 target genes; (3) increased HIF-1alpha acetylation 
      level; and (4) diminished sirtuin 1 expression (both protein and mRNA). Sirtuin 1 
      involvement in the regulation of HIF-1alpha level was confirmed applying cells with 
      silenced Sirt1 gene. Moreover, the presence of membrane MT1 and MT2 receptors was 
      identified in HK-2 cells and their ligand, ramelteon, turned out to mimic 
      melatonin action on both HIF-1alpha and sirtuin 1 levels. Thus, it is concluded that 
      the mechanism of melatonin-evoked decline in HIF-1alpha content in renal proximal 
      tubular cells involves increased acetylation of this subunit which results from 
      the attenuated expression of sirtuin 1, an enzyme reported to deacetylate HIF-1alpha. 
      This observation provides a new insight to the understanding of melatonin action 
      in kidneys.
CI  - Copyright (c) 2021 Owczarek, Gieczewska, Polanska, Paterczyk, Gruza and Winiarska.
FAU - Owczarek, Aleksandra
AU  - Owczarek A
AD  - Department of Metabolic Regulation, Faculty of Biology, Institute of 
      Biochemistry, University of Warsaw, Warsaw, Poland.
FAU - Gieczewska, Katarzyna B
AU  - Gieczewska KB
AD  - Department of Plant Anatomy and Cytology, Faculty of Biology, Institute of 
      Experimental Plant Biology and Biotechnology, University of Warsaw, Warsaw, 
      Poland.
FAU - Polanska, Marta
AU  - Polanska M
AD  - Department of Animal Physiology, Faculty of Biology, Institute of Functional 
      Biology and Ecology, University of Warsaw, Warsaw, Poland.
FAU - Paterczyk, Bohdan
AU  - Paterczyk B
AD  - Laboratory of Electron and Confocal Microscopy, Faculty of Biology, University of 
      Warsaw, Warsaw, Poland.
FAU - Gruza, Andrzej
AU  - Gruza A
AD  - Department of Metabolic Regulation, Faculty of Biology, Institute of 
      Biochemistry, University of Warsaw, Warsaw, Poland.
FAU - Winiarska, Katarzyna
AU  - Winiarska K
AD  - Department of Metabolic Regulation, Faculty of Biology, Institute of 
      Biochemistry, University of Warsaw, Warsaw, Poland.
LA  - eng
PT  - Journal Article
DEP - 20210114
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC7841413
OTO - NOTNLM
OT  - HK-2 cells
OT  - hypoxia
OT  - hypoxia-inducible factor-1
OT  - kidney
OT  - melatonin
OT  - sirtuin 1
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/02 06:00
MHDA- 2021/02/02 06:01
PMCR- 2021/01/14
CRDT- 2021/02/01 05:54
PHST- 2020/06/15 00:00 [received]
PHST- 2020/12/17 00:00 [accepted]
PHST- 2021/02/01 05:54 [entrez]
PHST- 2021/02/02 06:00 [pubmed]
PHST- 2021/02/02 06:01 [medline]
PHST- 2021/01/14 00:00 [pmc-release]
AID - 10.3389/fphys.2020.572911 [doi]
PST - epublish
SO  - Front Physiol. 2021 Jan 14;11:572911. doi: 10.3389/fphys.2020.572911. eCollection 
      2020.